Glial cell line-derived neurotrophic factor reverses toxin-induced injury to midbrain dopaminergic neurons in vivo

Barry J. Hoffer, Alex Hoffman, Kate Bowenkamp, Peter Huettl, John Hudson, David Martin, Leu Fen H. Lin, Greg A. Gerhardt

Research output: Contribution to journalArticlepeer-review

400 Scopus citations

Abstract

Fischer 344 rats were unilaterally injected into the medial forebrain bundle with 6-hydroxydopamine (6-OHDA). Apomorphine-induced rotational behavior was used to select animals whose rotation exceeded 300 turns/h, corresponding to greater than 95% dopamine (DA) depletion in the ipsilateral striatum. Four weeks later, glial cell line-derived neurotrophic factor (GDNF) or vehicle was injected intranigrally ipsilateral to the lesion (0.1-100 μg). The highest dose of GDNF tested produced a marked decrease in rotational behavior. This dose also produced levels of DA in the ipsilateral substantia nigra (SN) which were not statistically different from the contralateral side. Vehicle-treated animals showed a marked DA depletion in the ipsilateral SN. These results demonstrate neurochemical and behavioral improvements in unilaterally DA-lesioned rats following intranigral administration of GDNF, suggesting that GDNF may develop into a useful therapy for Parkinson's disease.

Original languageEnglish
Pages (from-to)107-111
Number of pages5
JournalNeuroscience Letters
Volume182
Issue number1
DOIs
StatePublished - Nov 21 1994

Keywords

  • 6-Hydroxydopamine
  • Dopamine
  • Glial cell line-derived neurotrophic factor
  • Parkinson's disease
  • Substantia nigra
  • Trophic factor

ASJC Scopus subject areas

  • General Neuroscience

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